About

Anthony Shoji Hall is an Associate Professor at the University of Pennsylvania. His research focuses on catalysis, particularly studying atomic ordering and ensemble effects in alloy electrocatalysts. He has developed strategies to investigate ensembles in catalysis without altering the electronic structure, exemplified by his work on tuning atomic ordering in Pd₃Bi alloys to control methanol electro-oxidation activity. His contributions include demonstrating how ensemble size alone can switch catalytic activity on or off, highlighting the importance of atomic ordering-induced ensemble variation in governing electrocatalyst states. Hall actively engages with the scientific community, sharing insights and collaborating on topics related to electrocatalysis and materials chemistry.

Research topics

• Immunology
• Biology
• Cancer research
• Genetics

Selected publications

• Gene coexpression networks reveal a broad role for lncRNAs in inflammatory bowel disease

  JCI Insight · 2024-02-08 · 10 citations

  articleOpen access

  The role of long noncoding RNAs (lncRNAs) in disease is incompletely understood, but their regulation of inflammation is increasingly appreciated. We addressed the extent of lncRNA involvement in inflammatory bowel disease (IBD) using biopsy-derived RNA-sequencing data from a large cohort of deeply phenotyped patients with IBD. Weighted gene correlation network analysis revealed gene modules of lncRNAs coexpressed with protein-coding genes enriched for biological pathways, correlated with epithelial and immune cell signatures, or correlated with distal colon expression. Correlation of modules with clinical features uncovered a module correlated with disease severity, with an enriched interferon response signature containing the hub lncRNA IRF1-AS1. Connecting genes to IBD-associated single nucleotide polymorphisms (SNPs) revealed an enrichment of SNP-adjacent lncRNAs in biologically relevant modules. Ulcerative colitis-specific SNPs were enriched in distal colon-related modules, suggesting that disease-specific mechanisms may result from altered lncRNA expression. The function of the IBD-associated SNP-adjacent lncRNA IRF1-AS1 was explored in human myeloid cells, and our results suggested IRF1-AS1 promoted optimal production of TNF-α, IL-6, and IL-23. A CRISPR/Cas9-mediated activation screen in THP-1 cells revealed several lncRNAs that modulated LPS-induced TNF-α responses. Overall, this study uncovered the expression patterns of lncRNAs in IBD that identify functional, disease-relevant lncRNAs.

  PublisherOA PDFDOI

• The lncRNA LUCAT1 is elevated in inflammatory disease and restrains inflammation by regulating the splicing and stability of NR4A2

  Proceedings of the National Academy of Sciences · 2022 · 43 citations

  • Biology
  • Cancer research
  • Immunology

  The nuclear long non-coding RNA LUCAT1 has previously been identified as a negative feedback regulator of type I interferon and inflammatory cytokine expression in human myeloid cells. Here, we define the mechanistic basis for the suppression of inflammatory gene expression by LUCAT1. Using comprehensive identification of RNA-binding proteins by mass spectrometry as well as RNA immunoprecipitation, we identified proteins important in processing and alternative splicing of mRNAs as LUCAT1-binding proteins. These included heterogeneous nuclear ribonucleoprotein C, M, and A2B1. Consistent with this finding, cells lacking LUCAT1 have altered splicing of selected immune genes. In particular, upon lipopolysaccharide stimulation, the splicing of the nuclear receptor 4A2 (NR4A2) gene was particularly affected. As a consequence, expression of NR4A2 was reduced and delayed in cells lacking LUCAT1. NR4A2-deficient cells had elevated expression of immune genes. These observations suggest that LUCAT1 is induced to control the splicing and stability of NR4A2, which is in part responsible for the anti-inflammatory effect of LUCAT1. Furthermore, we analyzed a large cohort of patients with inflammatory bowel disease as well as asthma and chronic obstructive pulmonary disease. In these patients, LUCAT1 levels were elevated and in both diseases, positively correlated with disease severity. Collectively, these studies define a key molecular mechanism of LUCAT1-dependent immune regulation through post-transcriptional regulation of mRNAs highlighting its role in the regulation of inflammatory disease.

  PublisherOA PDFDOI

• IL-27 and TCR Stimulation Promote T Cell Expression of Multiple Inhibitory Receptors

  ImmunoHorizons · 2019-01-01 · 78 citations

  articleOpen access

  Abstract Inhibitory receptors (IR) are a diverse group of cell surface molecules that modulate T cell activation, but there are gaps in our knowledge of the cell-extrinsic factors that regulate their expression. The present study found that in vivo overexpression of IL-27 in mice led to increased T cell expression of PD-L1, LAG-3, TIGIT, and TIM-3. In vitro, TCR stimulation alone promoted expression of multiple IRs, whereas IL-27 alone induced expression of PD-L1. However, the combination of intermediate TCR stimulation and IL-27 resulted in synergistic induction of LAG-3, CTLA-4, and TIGIT. In vivo, infection with Toxoplasma gondii resulted in parasite-specific effector T cells that expressed high levels of IR, and at local sites of infection where IL-27 production was highest, IL-27 was required for maximal effector cell expression of PD-L1, LAG-3, CTLA-4, and TIGIT. Together, these results affirm the critical role of TCR signals in the induction of IR expression but find that during infection, IL-27 promotes T cell expression of IR.

  PublisherDOI

• Publisher Correction: Get the IL-17F outta here!

  Nature Immunology · 2019-02-01 · 2 citations

  erratumOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Low-Dose Interleukin-2 Ameliorates Colitis in a Preclinical Humanized Mouse Model

  Cellular and Molecular Gastroenterology and Hepatology · 2019-01-01 · 34 citations

  letterOpen access

  Inflammatory bowel disease (IBD) is associated with immune dysregulation triggered by environmental factors, microbial dysbiosis, and genetical susceptibility. Regulatory T cells (Tregs) are critical in controlling intestinal immune homeostasis and Treg deficiencies trigger intestinal inflammation.1Brunkow M.E. et al.Nat Genet. 2001; 27: 68-73Crossref PubMed Scopus (2023) Google Scholar, 2Bennett C.L. et al.Nat Genet. 2001; 27: 20-21Crossref PubMed Scopus (2639) Google Scholar Interleukin (IL)-2 is a key cytokine controlling differentiation, survival, and function of Tregs.3Klatzmann D. et al.Nat Rev Immunol. 2015; 15: 283-294Crossref PubMed Scopus (399) Google Scholar In contrast to conventional T cells (Tcon), Tregs exhibit higher sensitivity to IL-2 due to constitutive expression of CD25, the high-affinity subunit of the IL-2 receptor.3Klatzmann D. et al.Nat Rev Immunol. 2015; 15: 283-294Crossref PubMed Scopus (399) Google Scholar Low-dose (LD) IL-2 has been reported to selectively expand Tregs and used as a therapeutic strategy in chronic graft-versus-host disease, hepatitis C virus–induced vasculitis, systemic lupus erythematosus, and Wiskott-Aldrich syndrome.4He J. et al.Nat Med. 2016; 22: 991-993Crossref PubMed Scopus (365) Google Scholar, 5Koreth J. et al.N Engl J Med. 2011; 365: 2055-2066Crossref PubMed Scopus (826) Google Scholar, 6Saadoun D. et al.N Engl J Med. 2011; 365: 2067-2077Crossref PubMed Scopus (588) Google Scholar, 7Jyonouchi S. et al.Clin Immunol. 2017; 179: 47-53Crossref PubMed Scopus (24) Google Scholar Thus, we sought to investigate LD IL-2 as an IBD therapeutic using humanized mice. Similar to other disease settings,4He J. et al.Nat Med. 2016; 22: 991-993Crossref PubMed Scopus (365) Google Scholar, 5Koreth J. et al.N Engl J Med. 2011; 365: 2055-2066Crossref PubMed Scopus (826) Google Scholar, 6Saadoun D. et al.N Engl J Med. 2011; 365: 2067-2077Crossref PubMed Scopus (588) Google Scholar, 7Jyonouchi S. et al.Clin Immunol. 2017; 179: 47-53Crossref PubMed Scopus (24) Google Scholar LD IL-2 specifically activated peripheral blood and colonic lamina propria Tregs from patients with IBD in vitro (Supplementary Figure 1). To study the efficacy of LD IL-2 in a preclinical setting, we treated NSG mice reconstituted with healthy donor peripheral blood mononuclear cells with phosphate-buffered saline (PBS) or LD IL-2 (1.0 × 104 IU/day [10K]; 5.0 × 104 IU/day [50K]) (Figure 1A). On day 5 following immune reconstitution, colitis was induced by rectal application of 2,4-dinitrobenzene sulfonic acid. Mice receiving 10K IL-2 had reduced weight loss and reduced histology scores compared with mice treated with PBS or 50K IL-2 (Figure 1B and C). Phospho-flow analysis of STAT5 confirmed that 10K IL-2 specifically activated Tregs, whereas STAT5 phosphorylation was also detected in Tcons from mice receiving 50K IL-2 (Figure 1D). Expansion of Tregs was observed in blood, spleen, and colon of mice treated with either dose of IL-2 (Figure 1E). However, reduced body weight loss upon treatment with 10K IL-2 associated with Treg expansion in the absence of significant Tcon activation suggest that a therapeutic range of LD IL-2 is critical (Figure 1C–E). To evaluate the efficacy of LD IL-2 in a fully reconstituted humanized murine system, we developed NSG mice that lack murine MHCII but express human HLA-DQ8 (NSGIIDQ8 mice). Sixteen-week-old mice reconstituted with human healthy donor CD34+ hematopoietic stem cells at birth were sensitized with 2,4,6-trinitrobenzenesulfonic acid (TNBS) and treated with 10K IL-2 daily followed by induction of colitis with TNBS rectal challenge (Figure 2A). In contrast to mice treated with PBS, mice receiving LD IL-2 exhibited significant improvement in histological disease activity with a trend in reduced weight loss (Figure 2B and C). LD IL-2 was associated with significant expansion of human Tregs in the blood and spleen but not in the mesenteric lymph nodes or colon (Figure 2D and E). Correspondingly, no difference in the frequency of FOXP3-expressing T cells was detected using RNAscope analysis of paraffin-embedded colonic lamina propria sections (Supplementary Figure 2). The expansion of peripheral Tregs and improvement in disease activity in LD IL-2-treated mice was not attributed to alterations in the human immune reconstitution between groups (Figure 2F) or frequency of effector T or natural killer cells (Supplementary Figure 3). Tregs have been reported to suppress pathogenic effector T cell function and autoimmunity through both contact-dependent and contact-independent mechanisms.8Sakaguchi S. et al.Nat Rev Immunol. 2010; 10: 490-500Crossref PubMed Scopus (1794) Google Scholar CyTOF analysis of splenic CD25+ cells showed an increased frequency of FOXP3+ T cells in mice receiving LD IL-2 with majority of expanded cells falling within the CD45RO+FOXP3+ Treg cluster (Figure 2G). The majority of FOXP3+ Tregs that expanded after LD IL-2-treatment exhibited increased expression of molecules associated with Treg activation or function (HLA-DR, CD45RO, and CTLA4) or chemokines important for trafficking and migration to sites of inflammation (CCR4 and CCR6) (Figure 2H). Our data suggest that expansion and activation of memory Tregs might be critical clinical determinants. Taken together, our study demonstrates that LD IL-2 expands Tregs and ameliorates experimental colitis in humanized mice. While these data support a rationale for LD IL-2 in IBD therapy, the safety of long-term drug administration needs further investigation to ensure continued selective activation of Tregs over Tcons. Based on these promising results, we have initiated a phase 1b/2a clinical trial investigating the safety and therapeutic efficacy of LD IL-2 in patients with moderate to severe ulcerative colitis (NCT02200445). The authors thank the Harvard Digestive Disease Center for their core support services. Download .pdf (2.13 MB) Help with pdf files Supplemental Methods Download .pdf (.12 MB) Help with pdf files Supplemental Figures 1–4

  PublisherOA PDFDOI

• Get the IL-17F outta here!

  Nature Immunology · 2018-06-14 · 10 citations

  letter1st authorCorresponding
  PublisherDOI

• Cytokine- and TCR-Mediated Regulation of T Cell Expression of Ly6C and Sca-1

  The Journal of Immunology · 2018-01-22 · 73 citations

  articleOpen access

  Abstract Ly6C and Sca-1 (Ly6A/E) are Ly6 family GPI-anchored surface molecules that are differentially expressed by multiple immune populations. Ly6C expression has been used to distinguish short-lived effector CD4+ T cells from memory precursor effector cells, whereas Sca-1 has been used in the identification of CD8+ memory stem cells. This study examines the expression patterns of these molecules and establishes that, in vitro, IL-27, type I IFN, and IFN-γ are potent inducers of Ly6C and Sca-1 in naive mouse CD4+ and CD8+ T cells, whereas TGF-β limits their expression. The induction of Ly6C and Sca-1 by IL-27 and IFN-γ is dependent on STAT1, but not STAT3 or T-bet. In mouse splenocytes, at homeostasis, Ly6C and Sca-1 expression was not restricted to effector cells, but was also found at various levels on naive and memory populations. However, in response to infection with Toxoplasma gondii, pathogen-specific T cells expressed high levels of these molecules and in this context, endogenous IL-27 and IFN-γ were required for the expression of Ly6C but not Sca-1. Together, these findings highlight the TCR-dependent and cytokine-mediated signals that modulate T cell expression of Ly6C and Sca-1 in vitro and in vivo during infection.

  PublisherOA PDFDOI

• CD11c-Expressing Cells Affect Regulatory T Cell Behavior in the Meninges during Central Nervous System Infection

  The Journal of Immunology · 2017-04-08 · 36 citations

  articleOpen access

  Abstract Regulatory T cells (Tregs) play an important role in the CNS during multiple infections, as well as autoimmune inflammation, but the behavior of this cell type in the CNS has not been explored. In mice, infection with Toxoplasma gondii leads to a Th1-polarized parasite-specific effector T cell response in the brain. Similarly, Tregs in the CNS during T. gondii infection are Th1 polarized, as exemplified by their T-bet, CXCR3, and IFN-γ expression. Unlike effector CD4+ T cells, an MHC class II tetramer reagent specific for T. gondii did not recognize Tregs isolated from the CNS. Likewise, TCR sequencing revealed minimal overlap in TCR sequence between effector T cells and Tregs in the CNS. Whereas effector T cells are found in the brain parenchyma where parasites are present, Tregs were restricted to the meninges and perivascular spaces. The use of intravital imaging revealed that activated CD4+ T cells within the meninges were highly migratory, whereas Tregs moved more slowly and were found in close association with CD11c+ cells. To test whether the behavior of Tregs in the meninges is influenced by interactions with CD11c+ cells, mice were treated with anti–LFA-1 Abs to reduce the number of CD11c+ cells in this space. The anti–LFA-1 treatment led to fewer contacts between Tregs and the remaining CD11c+ cells and increased the speed of Treg migration. These data suggest that Tregs are anatomically restricted within the CNS, and their interaction with CD11c+ populations regulates their local behavior during T. gondii infection.

  PublisherOA PDFDOI

• IFNγ Signaling Endows DCs with the Capacity to Control Type I Inflammation during Parasitic Infection through Promoting T-bet+ Regulatory T Cells

  PLoS Pathogens · 2015-02-06 · 32 citations

  articleOpen access

  IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population.

  PublisherOA PDFDOI

• Diverse Roles for T-bet in the Effector Responses Required for Resistance to Infection

  The Journal of Immunology · 2015-01-03 · 50 citations

  articleOpen access

  The transcription factor T-bet has been most prominently linked to NK and T cell production of IFN-γ, a cytokine required for the control of a diverse array of intracellular pathogens. Indeed, in mice challenged with the parasite Toxoplasma gondii, NK and T cell responses are characterized by marked increases of T-bet expression. Unexpectedly, T-bet(-/-) mice infected with T. gondii develop a strong NK cell IFN-γ response that controls parasite replication at the challenge site, but display high parasite burdens at secondary sites colonized by T. gondii and succumb to infection. The loss of T-bet had a modest effect on T cell production of IFN-γ but did not impact on the generation of parasite-specific T cells. However, the absence of T-bet resulted in lower T cell expression of CD11a, Ly6C, KLRG-1, and CXCR3 and fewer parasite-specific T cells at secondary sites of infection, associated with a defect in parasite control at these sites. Together, these data highlight T-bet-independent pathways to IFN-γ production and reveal a novel role for this transcription factor in coordinating the T cell responses necessary to control this infection in peripheral tissues.

  PublisherOA PDFDOI

Frequent coauthors

• Karoline I. Gaede

  University of Lübeck

  12 shared

• Karina Stein

  University of Notre Dame

  12 shared

• Holger Heine

  German Center for Lung Research

  12 shared

• Christopher A. Hunter

  University of Pennsylvania

  11 shared

• Kasper Hoebe

  Johnson & Johnson (United States)

  10 shared

• John L. Johnson

  Johnson & Johnson (United States)

  10 shared

• Christian Herzmann

  Saarland University

  9 shared

• Tim Vierbuchen

  University of Massachusetts Chan Medical School

  7 shared

Education

• Ph.D., Materials Science and Engineering

  University of California, Berkeley

  2009

• M.S., Materials Science and Engineering

  University of California, Berkeley

  2005

• B.S., Materials Science and Engineering

  University of California, Berkeley

  2003